{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T04:44:47Z","timestamp":1789965887677,"version":"4.0.1"},"reference-count":34,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2014,8,30]],"date-time":"2014-08-30T00:00:00Z","timestamp":1409356800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"EU FP6","award":["LSHM-CT-2005-018833"],"award-info":[{"award-number":["LSHM-CT-2005-018833"]}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Obesity"],"published-print":{"date-parts":[[2015,1]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Elevated insulin and inflammatory cytokine levels in obesity may chronically activate signaling pathways regulating cardiac growth and contractility. Our aim was to examine the effect of obesity on cardiac PI3K isoform and Akt activation during left ventricular (LV) hypertrophy and heart failure.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Wild\u2010type mice were fed normal chow or high\u2010fat diet (HFD) for 2, 4, or 6 months. A subset of mice was subjected to chronic myocardial ischemia (MI).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Echocardiography revealed a progressive increase in LV mass, wall thickness, and diameters in obese mice. Systolic pump function was not impaired. Increased cardiac levels of PI3K\u03b3, phosphorylated Akt, GSK3\u03b2, and Epac were observed after HFD for 2 months but gradually declined and were normal or reduced after 6 months, paralleled by elevated PP2A and SOCS3 levels. MI resulted in heart failure, independent of obesity, but compensatory LV hypertrophy was absent in obese mice. Histochemical analyses revealed similar increases in cardiac fibrosis, inflammation, apoptosis, and angiogenesis in lean and obese mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our findings suggest that activation of Akt initially contributes to cardiac hypertrophy and that chronic metabolic and inflammatory stimulation and overexpression of inhibitory mediators decrease PI3K\u03b3\u2010mediated Akt signaling and blunt compensatory hypertrophy after MI.<\/jats:p><\/jats:sec>","DOI":"10.1002\/oby.20888","type":"journal-article","created":{"date-parts":[[2014,8,30]],"date-time":"2014-08-30T06:59:20Z","timestamp":1409381960000},"page":"90-99","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Differential PI3K signal transduction in obesity\u2010associated cardiac hypertrophy and response to ischemia"],"prefix":"10.1002","volume":"23","author":[{"given":"Bernhard","family":"Uns\u00f6ld","sequence":"first","affiliation":[{"name":"Department of Cardiology and Pulmonary Medicine University Medical Center of the Georg August University of Goettingen  Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Bremen","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Pulmonary Medicine University Medical Center of the Georg August University of Goettingen  Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Didi\u00e9","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Pulmonary Medicine University Medical Center of the Georg August University of Goettingen  Germany"},{"name":"Department of Pharmacology University Medical Center of the Georg August University of Goettingen  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